Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage

Martin K. Angele, Markus W. Knöferl, Martin G. Schwacha, Alfred Ayala, William G. Cioffi, Kirby I. Bland, Irshad H. Chaudry

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139 Scopus citations

Abstract

Studies indicate that macrophage immune responses in males are depressed after trauma-hemorrhage, whereas they are enhanced in females under such conditions. Nonetheless, the involvement of male and female sex steroids in this gender-dependent dimorphic immune response after trauma-hemorrhage remains unclear. To study this, male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5α-dihydrotestosterone (DHT), 17β- estradiol, or a combination of both steroid hormones for 14 days before soft tissue trauma (i.e., laparotomy) and hemorrhagic shock (35 ± 5 mmHg for 90 min followed by adequate fluid resuscitation) or a sham operation. Twenty- four hours later the animals were killed, plasma was obtained, and Kupffer cell and splenic and peritoneal macrophage cultures were established. For DHT-treated mice, we observed significantly decreased releases of the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6 by splenic macrophage (-50 and -57%, respectively) and peritoneal macrophage (-51 and - 52%, respectively) cultures after trauma-hemorrhage compared with releases by cultures of cells from mice subjected to a sham operation; in contrast, responses of splenic and peritoneal macrophage cultures from other groups subjected to trauma-hemorrhage did not change significantly. In addition, only DHT-treated animals exhibited increased Kupffer cell IL-6 release (+634%). The release of IL-10 in DHT-treated hemorrhaged animals was increased compared with that in sham-operated animals but was decreased in estrogen-treated mice under such conditions. These results suggest that male and female sex steroids exhibit divergent immunomodulatory properties with respect to cell-mediated immune responses after trauma-hemorrhage.

Original languageEnglish (US)
Pages (from-to)C35-C42
JournalAmerican Journal of Physiology - Cell Physiology
Volume277
Issue number1 46-1
StatePublished - Aug 5 1999
Externally publishedYes

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Keywords

  • Gender
  • Immune depression
  • Kupffer cells
  • Shock

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Angele, M. K., Knöferl, M. W., Schwacha, M. G., Ayala, A., Cioffi, W. G., Bland, K. I., & Chaudry, I. H. (1999). Sex steroids regulate pro- and anti-inflammatory cytokine release by macrophages after trauma-hemorrhage. American Journal of Physiology - Cell Physiology, 277(1 46-1), C35-C42.